Grant: Travel Awards - Institute Community Support

Acute respiratory distress syndrome (ARDS) and pulmonary arterial hypertension (PAH) are acute and chronic respiratory illnesses which share inflammation as an essential part of their development. ARDS is characterized by severe inflammation which can impair gas exchange and result in respiratory failure. In PAH, inflammation changes the structure of blood vessels in the lungs which increases back pressure to the right heart, potentially causing heart failure. Despite decades of research, there are no curative therapies for either condition. Animal studies have shown a potential for mesenchymal stem cells (MSCs) to reduce inflammation, promote tissue regeneration and improve survival. We believe that small particles released by MSCs, known as exosomes, may have similar beneficial effects without the risks of whole cell injections. The aims of this project are to evaluate the ability of exosomes to treat cell and animal models of ARDS and PAH, to identify the biologically active factors that may be mediating this protective property and, given this insight, explore ways to genetically modify the cargo in exosomes to enhance their effects. In cell experiments, labelled exosomes were taken up by cells and improved their migration. In animal studies, a mouse model of ARDS showed an improved barrier function in lungs and reduced markers of inflammation after exosome treatment. In the chronic model of PAH, rats showed a significant reduction in lung pressure from a single dose of exosomes after three weeks. These promising results suggest that exosomes may be a viable therapy for both ARDS and PAH. Future studies will identify and increase expression of packaged molecules that facilitate the protective effects of exosomes to enhance efficacy. If this cell-free therapy is proven beneficial, our research group is ideally positioned to move this potentially life-saving treatment into clinical trials with hopes of improving management for these devastating lung conditions.